분자영상 및 방사화학

  • [Cancers (Basel).] Inhibition of HIF-1α by Atorvastatin During 131 I-RTX Therapy in Burkitt's Lymphoma Model

    [Cancers (Basel).] Inhibition of HIF-1α by Atorvastatin During 131 I-RTX Therapy in Burkitt's Lymphoma Model 림프종 모델에서 131I-RTX 치료 중 아토르바스타틴에 의한 HIF-1α의 억제

    KIRAMS / 김은호, 고혜영, 김진수*

  • 출처
    Cancers (Basel).
  • 등재일
    2020 May 11
  • 저널이슈번호
    12(5):E1203. doi: 10.3390/cancers12051203.
  • 내용

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    Abstract
    Backgrounds: Radioimmunotherapy (RIT) serves as a targeted therapy for non-Hodgkin lymphomas (NHL). Although HIF(Hypoxia-inducible factors)-1α is an important biomarker during radiation therapy, its role in NHL is unclear. Atorvastatin (ATV) is used as a combination drug for chemotherapy.

    Methods: We investigated whether ATV downregulated tumor radio-resistance and enhanced the anticancer effect of 131I-RTX (rituximab) in Raji xenograft mouse models. First, the increased uptake and enhanced therapeutic effect of 131I-RTX by ATV was confirmed using molecular imaging in Raji xenograft subcutaneous model and orthotropic model with SPECT and IVIS images. Second, we examined the profile of differentially expressed miRNAs using miRNA array.

    Results: We found that miR-346 inhibited HIF-1α/VEGF (Vascular endothelial growth factor) during ATV combination therapy with 131I-RTX. The underlying mechanism of ATV involved induction of anti-angiogenesis and radiosensitivity by downregulating HIF-1α in Raji cells.

    Conclusion: Our findings suggested that combination therapy with ATV and 131I-RTX is a promising strategy for enhancing the potency of 131I-RTX therapy in poorly responding patients and those with radio-resistance.

     

     

    그림. 고지혈증 치료제인 아토르바스타틴을 방사성요오드가 표지된 리툭시맙과 동시에 투여했을 때 암 치료효과가 증진되었으며, 이는 최신 핵의학 분자영상 장비인 SPECT(단일광자단층촬영법)로 입증하였습니다.

     

    Affiliations

    Eun-Ho Kim  1   2 , Hae Young Ko  3   4 , A Ram Yu  5 , Hyeongi Kim  3 , Javeria Zaheer  3   6 , Hyun Ji Kang  3   6 , Young-Cheol Lim  3 , Kyung Deuk Cho  3 , Hyun-Yoo Joo  1 , Min Kyoung Kang  5 , Jae Jun Lee  5 , Seung-Sook Lee  7 , Hye Jin Kang  8 , Sang Moo Lim  3   9 , Jin Su Kim  3   6
    1 Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Korea.
    2 Department of Biochemistry, School of Medicine, Catholic University of Daegu, 33, 17-gil, Duryugongwon-ro, Nam-gu, Daegu 705-718, Korea.
    3 Division of RI Application, Korea Institute of Radiological and Medical Sciences (KIRAMS), 75 Nowon-ro, Nowon-gu, Seoul 01812, Korea.
    4 Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
    5 Laboratory Animal Center, Osong Medical Innovation Foundation, Osong, Chungbuk 28159, Korea.
    6 Radiologcial and Medico-Oncological Sciences, University of science and technology (UST), Seoul 01812, Korea.
    7 Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.
    8 Division of Hematology/Oncology, Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.
    9 Department of Nuclear Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.

  • 키워드
    131I; HIF-1α; RIT; VEGF; atorvastatin; lymphoma; radioimmunotherapy; rituximab.
  • 연구소개
    방사면역치료는 방사선치료 효과와 표적항체에 의한 면역작용 효과가 결합한 치료로서, 표적항체를 이용하여 암세포에만 방사선을 조사해 정상세포에 미치는 방사선 영향을 최소화하여 암 치료 효과가 높은 첨단 방사선치료 분야입니다. 암세포는 증식하는 과정에서 쉽게 저산소증 상태가 되는데, 저산소 상황에서는 방사선치료가 어려워지는 문제가 있습니다. 이 연구에서는 아토르바스타틴이 저산소 상황을 극복하여 방사면역치료 효과를 증진시킬 수 있을 뿐만 아니라 림프종 종양 세포를 살상하는 효과가 있어서 최종적으로 방사성요오드가 표지된 리툭시맙의 치료효과를 증진시킬 수 있음을 제시하고, 이 과정은 micro RNA 346이 증가했기 때문임을 밝혔습니다.
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